Coronaviral RNA-methyltransferases: function, structure and inhibition

0555984 - ÚOCHB 2023 RIV GB eng J - Článek v odborném periodiku
Nencka, Radim - Šilhán, Jan - Klíma, Martin - Otava, Tomáš - Kocek, Hugo - Krafčíková, Petra - Bouřa, Evžen
Coronaviral RNA-methyltransferases: function, structure and inhibition.
Nucleic Acids Research. Roč. 50, č. 2 (2022), s. 635-650. ISSN 0305-1048. E-ISSN 1362-4962
Grant CEP: GA ČR(CZ) GA21-25280S; GA MZd(CZ) NU20-05-00472; GA MŠMT(CZ) EF16_019/0000729
Institucionální podpora: RVO:61388963
Klíčová slova: structure guided design * SARS coronavirus * SARS-CoV-2 replication
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 14.9, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1093/nar/gkab1279

Coronaviral methyltransferases (MTases), nsp10/16 and nsp14, catalyze the last two steps of viral RNA-cap creation that takes place in cytoplasm. This cap is essential for the stability of viral RNA and, most importantly, for the evasion of innate immune system. Non-capped RNA is recognized by innate immunity which leads to its degradation and the activation of antiviral immunity. As a result, both coronaviral MTases are in the center of scientific scrutiny. Recently, X-ray and cryo-EM structures of both enzymes were solved even in complex with other parts of the viral replication complex. High-throughput screening as well as structure-guided inhibitor design have led to the discovery of their potent inhibitors. Here, we critically summarize the tremendous advancement of the coronaviral MTase field since the beginning of COVID pandemic.
Trvalý link: http://hdl.handle.net/11104/0330958